Role of kappa opiate receptor agonists in the initiation of feeding

Role of kappa opiate receptor agonists in the initiation of feeding

Morley J.E.; Levine A.S.; Grace M.; Kniep J.

Life Sciences 31(23): 2617-2626

1982

A role for the endogenous opiates and their receptors in the regulation of appetite has been suggested. The relative effects of ketocyclazocine (KC), cyclazocine and ethylketocyclazocine, all putative .kappa. opiate receptor agonists, and morphine, a putative .mu. receptor agonist, on food consumption were examined [in rats]. All the .kappa. agonists and morphine induced feeding when administered at 0800 h. KC failed to induce, while morphine suppressed, feeding during the nocturnal feeding period (2000 and 0200 h). KC and morphine suppressed starvation induced feeding when food was made available immediately after injection and had no effect when food was presented 2 and 4 h after injection. High doses of naloxone (5 mg/kg) suppressed KC induced feeding while enhancing high dose morphine (25 mg/kg) induced feeding. Repeated injections of KC or morphine for 5 days resulted in enhancement of the feeding response with initiation of feeding occurring earlier. Taken together with studies showing that the endogenous .kappa. ligand dynorphin enhances feeding, apparently, .kappa. agonists are endogenous initiators of feeding and .kappa. receptors are maximally saturated at times of food deprivation and during spontaneous feeding. The .mu. (or one of the other) opiate receptors evidently inhibit feeding due to their sedative effect and antagonism of this effect leads to enhancement of the feeding response. Evidently, .kappa. opiate receptors represent an important component of the natural feeding drive.